Brain research
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Interleukin-1 beta (IL-1β) is one of pro-inflammatory cytokines. Recent studies have shown that IL-1β impairs hippocampal neurogenesis, mediates proliferation and differentiation of multipotent neural precursor cells (NPCs), and exerts effects of anti-proliferation, anti-neurogenesis, and pro-gliogenesis on embryonic hippocampal NPCs. The aim of this study was to examine the effect of IL-1β on the differentiation of hippocampal NPCs into functional serotonergic neurons, which play important roles in the pathophysiology and treatment of depression. ⋯ After three passages and phenotyping, hippocampal NPCs were cultured in a differentiating medium with various concentrations (5, 10, and 20 ng/mL) of IL-1β for 7 days. At the endpoint, the serotonergic differentiation of hippocampal NPCs in IL-1β-treated cultures decreased in a dose-dependent manner and this effect was blocked by IL-1ra, an IL-1 receptor antagonist capable of blocking the effects of IL-1 by binding to the same receptor (IL-1R1) without triggering signaling; serotonin in the lysate of the differentiated hippocampal NPCs decreased in IL-1β-treated cultures; and levels of Bcl-2 and phosphorylated extracellular-regulated kinase (pERK) were also lower in differentiated hippocampal NPCs with IL-1β treatment. These results support the hypothesis that IL-1β is an important factor in the stress-associated neuropathology and psychopathology and has relevance to the treatment of depressive symptoms in patients with depression.
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The present study examines the brain-level representation and composition of meaning in scalar quantifiers (e.g., some), which have both a semantic meaning (at least one) and a pragmatic meaning (not all). We adopted a picture-sentence verification design to examine event-related potential (ERP) effects of reading infelicitous quantifiers for which the semantic meaning was correct with respect to the context but the pragmatic meaning was not, compared to quantifiers for which the semantic meaning was inconsistent with the context and no additional pragmatic meaning is available. In the first experiment, only pragmatically inconsistent quantifiers, not semantically inconsistent quantifiers, elicited a sustained posterior negative component. ⋯ We hypothesize that the sustained negativity reflects cancellation of the pragmatic inference and retrieval of the semantic meaning. In our second experiment, we found that the process of re-interpreting the quantifier was independent from lexico-semantic processing: the N400 elicited by lexico-semantic violations was not modulated by the presence of a pragmatic inconsistency. These findings suggest that inferential pragmatic aspects of meaning are processed using different mechanisms than lexical or combinatorial semantic aspects of meaning, that inferential pragmatic meaning can be realized rapidly, and that the computation of meaning involves continuous negotiation between different aspects of meaning.